This project has been mapping the brains regions involved in emotion recognition and regulation in health and disease using two different but related 'activation' methods. In one series of studies we have imaged depressed subjects and controls using 015 PET and fMRl while they perform key neuropsychological tasks specifically designed to activate and test the function of important brain regions. We have developed a facial emotion recognition paradigm, an emotional Stroop paradigm, and a sadness induction paradigm, in order to probe the neural networks involved in emotion recognition and emotion regulation. The second method involves actually stimulating the brain regions important in mood recognition or regulation and assessing differences in mood. This is done safely and effectively using rabid transcranial magnetic stimulation (rTMS). 1) We have demonstrated key brain regions involved in emotion recognition from several sensory modalities (faces, spoken language). 2) We have shown that clinically depressed subjects do not activate the limbic system in the same Way as controls during tasks which involve the limbic system or related areas (the right insula in face emotion recognition, the cingulate during the Stroop interference task). 3) During transient sadness, healthy adults activate the anterior limbic system. During happiness, they activate only the anterior cingulate and deactivate numerous areas in secondary association cortex. Women, compared to men, activate more of the limbic system, despite similar performance. 4) Depressed subjects, both while actively depressed and also when recently recovered and euthymic, have difficulty making themselves transiently happy or sad. 5) Stimulation of the left prefrontal cortex in healthy controls causes mild increases in sadness, with right increases in happiness. 6) Prefrontal, and not occipital, stimulation causes increases in serum TSH with no changes in prolactin or cortisol. 7) Chronic daily left prefrontal stimulation improves depressive symptoms in patients who are resistant to multiple antidepressant medications. 8) Left prefrontal stimulation produces both local and remote brain effects which can be demonstrated on FDG PET scanning.